The purposes of this project are to: 1. Further characterize the neurotransmitter regulation of ACTH release and the level at which it occurs (i.e. CNS or pituitary) by: (A) Investigating (in the rat) the interrelationships between the development of circadian periodicity of plasma corticosteroid levels, stress evoked cortisoteroid release, and elevated corticosteroid levels, and that of regional CNS content and turnover of acetylcholine. (B) The study (in dispersed pituitary cell preparations) of the direct effect of monoaminergic and cholinergic agents on ACTH release. 2. Investigate (by immunoassay and bioassay) the nature of ACTH released: (A) In vivo: in diseases affecting the human CNS-pituitary-adrenal axis, as well as under conditions of circadian variation, stress and feedback in both normal subjects and patients with pituitary and adrenal disease. (B) In vitro: in response to hypothalamic extracts and neurotransmitter agents. 3. Further study the circadian periodicity of plasma ACTH and corticosteroid levels to determine: (A) In the human, the physiological consequences of the absence of such periodicity. (B) In animals, whether temporary obliteration of such periodicity hastens its phase shifting.